Project Summary As part of an established core facility, we request a Zeiss LSM880 laser-scanning confocal microscope with Airyscan super-resolution module on an inverted microscope stand. Addressing multiple live-cell/tissue studies, our needs come from the desire to reduce photodamage of living cells, the desire to resolve molecular-level events, particularly in living cells, and the oversubscription on existing laser-scanning confocal instruments. Although we have many Zeiss laser-scanning confocals, they are heavily used, with the oldest effectively obsolete and unreliable. Although the Airyscan module on the LSM880 provides modest super-resolution, its greatest appeal is the combination of exceptional signal-to-noise performance, speed of imaging, flexibility to improve imaging of almost any microscope objective, and ease of use needed for our research projects. Not only are photodamage and photobleaching minimized, the Airyscan images can reveal subcellular features of living cells not visible with other commercial super-resolution or confocal microscopes. The proposed instrument will provide an order-of-magnitude superior performance that will enable key NIH-funded projects.